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HEMOGLOBIN HEMOGLOBIN

Each red cell contain hemoglobin ,Each red cell contain hemoglobin , which is a special protein which is a special protein Able to carry oxygen to the tissue Able to carry oxygen to the tissue & return CO& return CO22 from tissue to the lungs from tissue to the lungs

The binding of OThe binding of O22 to Hb is regulated to Hb is regulated by 2,3,diphosphoglycerate (2,3,DPG)by 2,3,diphosphoglycerate (2,3,DPG)

Hemoglobin concentration Hemoglobin concentration

Out of the total blood Percentage of Out of the total blood Percentage of RBCs is 40-45 % ( in normal subject )RBCs is 40-45 % ( in normal subject )

If the quantity of hemoglobin in each If the quantity of hemoglobin in each cell is normal the blood contain 15 cell is normal the blood contain 15 grams of hemoglobin in every 100 grams of hemoglobin in every 100 milliliters milliliters

HemoglobinHemoglobin

Hemoglobin is a conjugated globular Hemoglobin is a conjugated globular protein that constitutes 33% of the protein that constitutes 33% of the erythrocyte’s weight by volume. erythrocyte’s weight by volume.

Hemoglobin has a molecular weight of Hemoglobin has a molecular weight of 68,000 68,000 making it a large protein. making it a large protein.

Each normal erythrocyte contains Each normal erythrocyte contains 200-200-300300 million molecules of hemoglobin. million molecules of hemoglobin.

65% of hemoglobin synthesis occurs 65% of hemoglobin synthesis occurs during the nucleated stages of during the nucleated stages of maturation and 35% during the maturation and 35% during the reticulocyte stage.reticulocyte stage.

Normal valuesNormal values

Male: 13.5 to 18 g/dlMale: 13.5 to 18 g/dl Female: 11.5 to 16 g/dlFemale: 11.5 to 16 g/dl

Composition of hemoglobin:Composition of hemoglobin:

Each hemoglobin molecule consists of 4 Each hemoglobin molecule consists of 4 heme groups and 1 globin molecule. heme groups and 1 globin molecule.

EachEach Heme Heme group contains a group contains a protoporphyrin ring plus an iron molecule. protoporphyrin ring plus an iron molecule.

EachEach Globin Globin consists of 4 polypeptide consists of 4 polypeptide chains (2 pairs). chains (2 pairs).

The synthesis of protoporphyrin and The synthesis of protoporphyrin and globin is coordinated, so if production of globin is coordinated, so if production of one decreases the production of the other one decreases the production of the other also decreases.also decreases.

Globin formationGlobin formation

The polypeptide chains of globin are produced on The polypeptide chains of globin are produced on the the Ribosomes.Ribosomes.

The four most common chain types are alpha, The four most common chain types are alpha, beta, gamma and delta chains.beta, gamma and delta chains.

Each of these chains differs from the others in Each of these chains differs from the others in their amino acid sequence. their amino acid sequence.

Each globin molecule is made of 2 pairs of chains Each globin molecule is made of 2 pairs of chains and each chain is made of 141-146 amino acids and each chain is made of 141-146 amino acids

Heme formationHeme formation

Heme formation takes place in the Heme formation takes place in the Mitochondria Mitochondria then the cytoplasm of then the cytoplasm of erythroid precursors through the erythroid precursors through the reticulocyte stage. reticulocyte stage.

It begins with production of a It begins with production of a protoporphyrin ring.protoporphyrin ring.

Iron then incorporates with Iron then incorporates with protoporphyrin to form heme.protoporphyrin to form heme.

ConfigurationConfiguration

The polypeptide chains of adult The polypeptide chains of adult hemoglobin are organized into 2 alpha hemoglobin are organized into 2 alpha chains and 2 beta chains; each chain chains and 2 beta chains; each chain has an attached heme group. has an attached heme group.

In this configuration hemoglobin carries In this configuration hemoglobin carries its maximum amount of O2; if the its maximum amount of O2; if the hemoglobin molecule is denatured hemoglobin molecule is denatured (altered) it looses its ability to carry O(altered) it looses its ability to carry O22..

complete hemoglobincomplete hemoglobin

A complete hemoglobin molecule is A complete hemoglobin molecule is spherical, has 4 heme groups spherical, has 4 heme groups attached to the 4 polypeptide chains attached to the 4 polypeptide chains so it may carry up to 4 molecules of so it may carry up to 4 molecules of O2.O2.

Heme is suspended between Heme is suspended between portions of a polypeptide chain.portions of a polypeptide chain.

Synthesis of hemoglobinSynthesis of hemoglobinsynthesis of hemoglobin occur in the mitochondria of the developing red cell

Glycine + succinyl – CoA alpha aminolaevulinic acid

pyrrol ring

Alpha aminolaevulinic acid Synthetase

4 pyrrole protoporphyrine

protoporphyrine + Fe Heme

Heme + polypeptide hemoglobine chain ( alpha or beta )

2 alpha chains + 2 beta chains hemoglobin A

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Structure of haemoglobine Structure of haemoglobine

fetal hemoglobin fetal hemoglobin (hemoglobin (hemoglobin F)F)

fetal hemoglobin (hemoglobin F) is fetal hemoglobin (hemoglobin F) is present in fetal blood during the 5th present in fetal blood during the 5th week through the 9th month of week through the 9th month of gestation and after birth. gestation and after birth.

The switch to adult hemoglobin in The switch to adult hemoglobin in not complete for 3 to 6 months. not complete for 3 to 6 months.

Hemoglobin F functions very well in Hemoglobin F functions very well in the low O2 environment in the uterus the low O2 environment in the uterus because its affinity for O2 is higher because its affinity for O2 is higher than normal adult hemoglobin. than normal adult hemoglobin.

adult hemoglobin adult hemoglobin (hemoglobin (hemoglobin AA))

adult hemoglobin (hemoglobin A) is adult hemoglobin (hemoglobin A) is made of 2 alpha and 2 beta chains. made of 2 alpha and 2 beta chains.

It makes up 95 to 97% of adult It makes up 95 to 97% of adult hemoglobin. hemoglobin.

Adult erythrocytes also contain Adult erythrocytes also contain hemoglobin A2 (2 alpha and hemoglobin A2 (2 alpha and 2 delta2 delta chainschains) and hemoglobin F. ) and hemoglobin F.

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plasmaplasma

• Color Color

Plasma is a pale yellow fluidPlasma is a pale yellow fluid

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VolumeVolume

• slightly slightly more than more than half the half the total blood total blood volumevolume

• 55% of total55% of total blood blood volume volume

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plasma is considered plasma is considered colloidal solution colloidal solution

(fine particles suspended in a (fine particles suspended in a liquid & resistant to liquid & resistant to sedimentation or filtration)sedimentation or filtration)

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Colloidal solution.

Composition of plasma Composition of plasma

Plasma contain proteins Plasma contain proteins • ALBUMIN ,ALBUMIN ,• GLOBULINES , GLOBULINES , • & & • FIBRINOGINE FIBRINOGINE

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SERUMSERUM

when proteins that when proteins that produce clots are produce clots are removed from plasma , removed from plasma , the remaining fluid is the remaining fluid is called serum.called serum.

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Other components Other components

In addition to suspended molecules plasma also In addition to suspended molecules plasma also contain a number of dissolved components such contain a number of dissolved components such asas

• SALTS, SALTS, • NUTRIENTS , NUTRIENTS , • GASES , GASES , • WASTE PRODUCTS , WASTE PRODUCTS , • HORMONS , HORMONS , • & ENZYMES& ENZYMES

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Solutes in plasma comes from several Solutes in plasma comes from several sources such as sources such as liver, kidney, liver, kidney, intestine , endocrine glands , intestine , endocrine glands ,

& immune tissue& immune tissue such as spleen.such as spleen.Under normal condition the intake of Under normal condition the intake of

both water & solute into the body both water & solute into the body equals the output equals the output

so that the total volumes in the body so that the total volumes in the body are maintained within a narrow range are maintained within a narrow range

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Composition of plasma Composition of plasma Plasma Plasma componentscomponents

%% Functions Functions

waterwater 91.591.5 Act as solvent & suspending medium Act as solvent & suspending medium for blood components for blood components

Proteins Proteins 77

Albumin Albumin 5555 Viscosity. osmotic pressure Viscosity. osmotic pressure buffer buffer

Globulin Globulin 3838 Antibody Antibody

Fibrinogen Fibrinogen 44 clottingclotting

ComplementComplementss

11 Part of immune systemPart of immune system

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Composition of plasmaComposition of plasmaIons Ions Na, K, Ca, CL, Na, K, Ca, CL,

F,H,HcoF,H,Hco3.3.

0.90.9 Osmotic pressure membrane potential & Osmotic pressure membrane potential & acid bas balance acid bas balance

Nutrients Nutrients Glucose, vitamins, Glucose, vitamins, cholesterol ,triglycecholesterol ,triglyce

ride, amino acids.ride, amino acids.

0.30.3 Source of energy & basic building Source of energy & basic building block of complex molecules block of complex molecules

Gases. Gases. CoCo2.2.

0.10.1 Waste product of aerobic Waste product of aerobic metabolismmetabolism

OO2.2. 0.10.1 Necessary for aerobic metabolismNecessary for aerobic metabolism

Nitrogen, Nitrogen, Urea, Urea, ammonia ammonia

0.10.1 Break down products of protein Break down products of protein metabolismmetabolism

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PolycythemiaPolycythemia

PolycythemiaPolycythemia is a condition in which is a condition in which there is a net increase in the total there is a net increase in the total number of red blood cells in the body. number of red blood cells in the body.

The overproduction of red blood cells The overproduction of red blood cells may be due to a primary process in may be due to a primary process in the bone marrow (the bone marrow (a so-called a so-called myeloproliferative syndrome),myeloproliferative syndrome),

or it may be a reaction to chronically or it may be a reaction to chronically low oxygen levels or, rarely, a low oxygen levels or, rarely, a malignancy.malignancy.

Primary polycythemia Primary polycythemia (Polycythemia vera)(Polycythemia vera)

Primary polycythemiaPrimary polycythemia, often called , often called polycythemia verapolycythemia vera (PCV), polycythemia (PCV), polycythemia rubra vera (PRV), or erythremia, occurs rubra vera (PRV), or erythremia, occurs when excess red blood cells are produced when excess red blood cells are produced as a result of an abnormality of the as a result of an abnormality of the bone marrow..

Often, excess Often, excess white blood cells and and platelets are also produced. are also produced.

Polycythemia vera is classified as a Polycythemia vera is classified as a myeloproliferative disease..

Epidemiology Epidemiology Polycythemia vera occurs in all age Polycythemia vera occurs in all age

groups (including children although the groups (including children although the incidence increases with age.incidence increases with age.

One study found the median age at One study found the median age at diagnosis to be 60 years,diagnosis to be 60 years,

and the disease is more common in men and the disease is more common in men than women. than women.

Symptoms Symptoms Patients with polycythemia vera are Patients with polycythemia vera are

often often asymptomatic.. A classic symptom of polycythemia A classic symptom of polycythemia

vera is generalized itching, vera is generalized itching, particularly after exposure to warm particularly after exposure to warm water, which may be due to water, which may be due to abnormal histamine release or abnormal histamine release or prostaglandin productionprostaglandin production

Such itching is present in Such itching is present in approximately 40% of patients with approximately 40% of patients with polycythemia vera. polycythemia vera.

A rare but classic symptom of A rare but classic symptom of polycythemia vera is erythromelalgiapolycythemia vera is erythromelalgia

This is a sudden, severe burning pain in This is a sudden, severe burning pain in the hands or feet, usually accompanied the hands or feet, usually accompanied by a reddish or bluish coloration of the by a reddish or bluish coloration of the skin.skin.

Erythromelalgia is caused by an Erythromelalgia is caused by an increased platelet count or increased increased platelet count or increased platelet "stickiness", resulting in the platelet "stickiness", resulting in the formation of tiny blood clots in the formation of tiny blood clots in the vessels of the extremity; vessels of the extremity;

it responds rapidly to treatment with it responds rapidly to treatment with aspirin.aspirin.

Secondary polycythemia Secondary polycythemia Secondary polycythemia is caused by either natural or Secondary polycythemia is caused by either natural or

artificial increases in the production of erythropoietin artificial increases in the production of erythropoietin that result in an increased production of erythrocytes. that result in an increased production of erythrocytes.

In secondary polycythemia, there may be 6 to 8 million In secondary polycythemia, there may be 6 to 8 million and occasionally 9 million erythrocytes per cubic and occasionally 9 million erythrocytes per cubic millimeter of blood.millimeter of blood.

A type of secondary polycythemia in which the A type of secondary polycythemia in which the production of erythropoietin increases appropriately is production of erythropoietin increases appropriately is called physiologic polycythemia. called physiologic polycythemia.

Physiologic polycythemia occurs in individuals living at Physiologic polycythemia occurs in individuals living at high altitudes, where oxygen availability is less than at high altitudes, where oxygen availability is less than at sea level. sea level.

Many athletes train at higher altitudes to take Many athletes train at higher altitudes to take advantage of this effect — a legal form of blood doping.advantage of this effect — a legal form of blood doping.

Actual polychthemia sufferers have been known to use Actual polychthemia sufferers have been known to use their condition as an athletic advantage for greater their condition as an athletic advantage for greater stamina.stamina.

Other causes of secondary polycythemiaOther causes of secondary polycythemia

Other causes of secondary Other causes of secondary polycythemia includepolycythemia include

smoking,smoking, renal or liver tumors, renal or liver tumors, heart or lung diseases that result in heart or lung diseases that result in

hypoxia. hypoxia. Athletes and bodybuilders who abuse Athletes and bodybuilders who abuse

anabolic steroids or erythropoietin anabolic steroids or erythropoietin may develop secondary may develop secondary polycythemia.polycythemia.